BACKGROUND: In hepatitis C virus infection an inappropriate ratio of pro-inflammatory and anti-inflammatory cytokines may either determine different outcomes of the infection or affect the benefit of antiviral treatment. Given that polymorphisms in regulatory regions of cytokine genes influence cytokine production, we determined frequency of polymorphisms of IL-10, IFNgamma, and TNFalpha genes in HCV-infected patients and healthy controls, and investigated their association with either ongoing or cleared HCV infection, or with response to treatment. METHODS: Genomic DNA from 270 patients and 145 controls sharing the same ethnic background was studied by polymerase chain reaction, restriction enzyme digestion, direct sequencing, and microsatellite analysis. RESULTS: The IL-10 ATA haplotype was more frequent in patients with spontaneous HCV RNA clearance (36.0%) than in patients with persistent infection (23%) (p=0.009, p corrected = 0.036). Neither TNF -308 and -238 polymorphisms nor IFNgamma alleles variability were associated with different HCV outcome. However, the combination of ATA homozygous state and IFNgamma 119 allele was more frequent in patients with spontaneous HCV clearance than in patients with ongoing disease (p=0.012; p corrected = 0.048). We could not confirm the reported effect of genetic influence on the response to treatment. CONCLUSIONS: Our findings indicate that heterogeneity in the promoter region of the IL-10 gene has a role in determining a spontaneous favourable outcome of HCV infection.
BACKGROUND: In hepatitis C virus infection an inappropriate ratio of pro-inflammatory and anti-inflammatory cytokines may either determine different outcomes of the infection or affect the benefit of antiviral treatment. Given that polymorphisms in regulatory regions of cytokine genes influence cytokine production, we determined frequency of polymorphisms of IL-10, IFNgamma, and TNFalpha genes in HCV-infectedpatients and healthy controls, and investigated their association with either ongoing or cleared HCV infection, or with response to treatment. METHODS: Genomic DNA from 270 patients and 145 controls sharing the same ethnic background was studied by polymerase chain reaction, restriction enzyme digestion, direct sequencing, and microsatellite analysis. RESULTS: The IL-10 ATA haplotype was more frequent in patients with spontaneous HCV RNA clearance (36.0%) than in patients with persistent infection (23%) (p=0.009, p corrected = 0.036). Neither TNF -308 and -238 polymorphisms nor IFNgamma alleles variability were associated with different HCV outcome. However, the combination of ATA homozygous state and IFNgamma 119 allele was more frequent in patients with spontaneous HCV clearance than in patients with ongoing disease (p=0.012; p corrected = 0.048). We could not confirm the reported effect of genetic influence on the response to treatment. CONCLUSIONS: Our findings indicate that heterogeneity in the promoter region of the IL-10 gene has a role in determining a spontaneous favourable outcome of HCV infection.
Authors: Ying Huang; Huiying Yang; Brian B Borg; Xiaowen Su; Shannon L Rhodes; Kai Yang; Xiaomei Tong; George Tang; Charles D Howell; Hugo R Rosen; Chloe L Thio; David L Thomas; Harvey J Alter; Ronda K Sapp; T Jake Liang Journal: Proc Natl Acad Sci U S A Date: 2007-01-10 Impact factor: 11.205